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S M Crawford

Publications and source records attributed to S M Crawford.

8 recordsLinked to original sources

Phase II trials of fosquidone, (GR63178A), in colorectal, renal and non-small cell lung cancer. CRC Phase II Clinical Trials Committee.

A total of 61 eligible patients with metastatic cancer have been treated in a series of Phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were colorectal (23), renal (21), and non small cell lung (17). No patient had received prior chemotherapy. The drug was given intravenously as a 20 min infusion at the dose of 120 mg-2 on days 1 to 5 every 3 weeks. Treatment was well tolerated; the only significant side effects being mild nausea and generalised musculo-skeletal pains. Response was assessed after two cycles of therapy. No patient achieved an objective partial response. A total of nine patients demonstrated stable disease for a median duration of 11 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.

Adult

The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.

We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed.

Adenocarcinoma

Metabolic and anthropometric changes with weight cycling in wrestlers.

Repeated cycles of weight loss and regain have come to be known as weight cycling. This phenomenon is frequently observed in athletes who must meet specific weight categories to qualify for competition. The purpose of this study was to determine the metabolic and anthropometric changes that occur with rapid weight loss/regain cycles in competitive wrestlers. Collegiate wrestlers were divided into two groups, "cyclers" (N = 8) and "noncyclers" (N = 6), based on their reported dieting history. Measurements included a 3-d diet record, resting energy expenditure (REE), skinfold and girth measures, and biochemical tests at three time points: preseason, peak season, and off-season. All anthropometric measures changed with time, and a diet group by time interaction was observed for the trunk to extremity skinfolds ratio (T/E) (P < 0.05), with greater fat loss and regain from the trunk area of the cyclers. There were no differences in REE within or between groups. Serum triiodothyronine (T3) values decreased over time (P < 0.01). Large weight losses appear to have occurred due to both dieting and short-term dehydration, and although physiological changes were observed, a training effect may have overridden any metabolic influence of weight cycling.

Adult

A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy.

A total of 24 patients who were receiving combination chemotherapy (POMB) including cisplatin at a dose of 100-120 mg/m2 were treated with the 5HT3 antagonist GR38032F (GR) as an anti-emetic prophylaxis. GR was given as a 15-min loading infusion followed by a 24-h infusion at three escalating dose levels of 1, 2 and 4 mg/h. In the first 24 h after commencing treatment, six patients had complete control of nausea and vomiting (CR), two had 1-2 emetic episodes (MR) and five had 3-5 emetic episodes (mR). The major response rate (CR + MR) was thus 35%. Eight responding patients (CR or MR) went on to receive oral GR at 8 or 12 mg t.i.d. for 5 days. In this group there was one CR, one MR, two mRs and four failures (F). There was no evidence of an improved therapeutic effect with increasing dose in either the infusion or the oral section of the study, although numbers were limited in the latter part of the trial. Toxicity was mild, with low-grade headache affecting 25% of patients being the most frequent side effect. Pharmacokinetic data was obtained in six patients at each dose level. There was a progressive rise in clearance with increasing dose, indicating that the kinetics are non-linear. However, there was no evidence of an association between high plasma levels and therapeutic efficacy. GR38032F is well tolerated and has promising single-agent activity in preventing vomiting induced by high-dose cisplatin.

Adult

Treatment of bladder carcinoma using a germ cell chemotherapy protocol.

Elevated levels of circulating beta-human chorionic gonadotrophin (beta-HCG) are commonly associated with a variety of tumours of germ cell origin. Other carcinomas may possess choriocarcinomatous elements but only rarely have there been reports of transitional cell carcinomas of the bladder associated with raised germ cell tumour markers, possibly because assays are not routinely performed. We present 3 patients with advanced transitional cell carcinoma of the bladder, 2 with metastatic and 1 with locally invasive disease, who had raised levels of germ cell tumour markers. These patients were therefore treated with combination chemotherapy appropriate to such tumours, with excellent results, as shown by clinical improvement and return to normal of tumour marker levels. Recent reports of the association between bladder carcinoma and ectopic synthesis of beta-HCG are reviewed. It was concluded that the production of beta-HCG is probably not rare, but that when it is found, the adoption of an appropriate chemotherapeutic regime may be successful.

Antineoplastic Combined Chemotherapy Protocols

"Salt tablets".

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